tag:theconversation.com,2011:/africa/topics/amoeba-5817/articlesAmoeba – The Conversation2018-02-26T11:16:11Ztag:theconversation.com,2011:article/906102018-02-26T11:16:11Z2018-02-26T11:16:11ZPlague bacteria may be hiding in common soil or water microbes, waiting to emerge<figure><img src="https://images.theconversation.com/files/207585/original/file-20180222-152375-1m2bpf6.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Children at a school in Antananarivo, Madagascar, during a plague outbreak, Oct. 3, 2017. </span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Madagascar-Plague/53f6b085f3874bcbac5722f0a919c8c8/64/0">AP Photo/Alexander Joe, File</a></span></figcaption></figure><p>Plague is a highly contagious disease that has killed millions of people over the past 1,400 years. Outbreaks still sporadically occur in as many as <a href="http://www.who.int/mediacentre/factsheets/fs267/en">36 countries worldwide</a>. Perhaps one of the greatest remaining mysteries surrounding plague is how and where it survives between outbreaks.</p>
<p>Like many other pathogens, the bacteria that causes plague, <em>Yersinia pestis</em>, <a href="https://doi.org/10.1051/vetres:2008039">cannot survive for long periods of time</a> in the environment without protection. Despite this, plague outbreaks continually recur in many locations. This suggests that the bacteria are able to find refuge and survive for several years after an outbreak before <a href="https://doi.org/10.1093/biosci/biv179">reappearing, seemingly out of nowhere</a>, and starting another infection cycle. Understanding where they hide and how they survive and reappear is extremely important for preventing future outbreaks.</p>
<p>Our recent <a href="http://dx.doi.org/10.3201/eid2402.171065">study</a> conducted at Colorado State University’s <a href="https://vpr.colostate.edu/idrc/">Infectious Disease Research Center</a> shows that amoebae – common soil and waterborne microorganisms that eat bacteria – could play a role in protecting this dangerous pathogen between outbreaks. This relationship may give plague bacteria a place to replicate and bide their time before conditions are right for another outbreak to occur.</p>
<h2>An ancient and mysterious killer</h2>
<p>Plague has caused <a href="http://dx.doi.org/10.1146/annurev.ento.50.071803.130337">three deadly worldwide pandemics</a>. <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027546,00.html">The Plague of Justinian</a> killed millions of people in the Byzantine Empire between the years 541 and 750. Next, the notorious <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027547,00.html">Black Death</a> ravaged much of Asia and Europe from 1330 to 1480, killing approximately 30 percent of all Europeans. Most recently, plague reappeared in <a href="http://content.time.com/time/specials/packages/article/0,28804,2027479_2027486_2027498,00.html">China</a> in 1855 and spread to ports worldwide over the following century, killing some 12 million people. Thousands of small outbreaks have occurred between and following these events. </p>
<p>Part of what makes understanding plague so difficult is its ability to infect <a href="https://pubs.usgs.gov/circ/1372">over 250 mammals and many species of insects</a> via multiple routes of transmission. For example, it can be transmitted through a bite from an infected flea or by inhaling bacteria coughed up by an infected animal.</p>
<p>Plague outbreaks also occur across very diverse environments. They range from prairie ecosystems in the western United States to highland forests in central Madagascar and temperate deserts in western China. The fact that few characteristics unify all of these regions may indicate that plague bacteria use <a href="https://doi.org/10.1371/journal.pntd.0004949">different survival mechanisms in each location</a>. However, one unifying factor is the presence of amoebae in the soil.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" srcset="https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=350&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=350&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=350&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=440&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=440&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/207694/original/file-20180223-108125-1kch2rz.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=440&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">World Health Organization 2016</span></span>
</figcaption>
</figure>
<h2>Abundant hosts</h2>
<p>Amoebae are single-celled microorganisms that live in almost all soils and water bodies across the globe. They feed on bacteria, but scientists have discovered that some bacteria are <a href="http://dx.doi.org/10.1128/CMR.17.2.413-433.2004">resistant to being digested by amoebae</a>. Interestingly, they include <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811209/">plague’s most closely related ancestors</a>, <em>Y. pseudotuberculosis</em> and <em>Y. enterocolitica</em>. </p>
<p>Living in the soil, alongside amoebae, required these bacteria to evolve ways to avoid being eaten. Given this evolutionary history, our research team hypothesized that when plague evolved from <em>Y. pseudotuberculosis</em> approximately 10,000 to 40,000 years ago, it may have retained the ability to survive inside amoebae.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" srcset="https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=424&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=424&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/207697/original/file-20180223-108125-fk499u.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=424&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<h2>Natural disease incubators</h2>
<p>To test our hypothesis we collected soil samples from prairie dog burrows in northeastern Colorado because prairie dogs are known hosts of plague. This involved finding prairie dog colonies that were experiencing a plague outbreak and inserting a long flexible probe into burrows to collect samples from deep within, while avoiding potentially infectious fleas emerging from the burrow. After isolating amoebae from the soil in our lab, we identified five species to use in future experiments.</p>
<p>The next step was to determine how plague bacteria interacted with the various amoeba species we identified. In a special high-containment laboratory, designed to prevent dangerous pathogens from accidentally escaping, we combined amoebae and various strains of plague bacteria obtained from the U.S. Centers for Disease Control’s <a href="http://co-labs.org/labs?id=3">laboratory</a> in Fort Collins, Colorado. We used a genetically altered strain of plague that fluoresces neon green to determine if and when amoebae were ingesting plague bacteria by viewing them under a high- powered microscope.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" srcset="https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=457&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=457&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=457&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=574&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=574&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/207695/original/file-20180223-108122-69frpw.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=574&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fluorescent plague bacteria inside amoebae. Scale bar indicates 30 microns.</span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<p>Next we used a transmission electron microscope to obtain even more detailed images of the inside of infected amoebae. This revealed that the plague bacteria were alive and possibly replicating. To confirm this, we selectively cracked open the infected amoebae at different time points to compare the number of bacteria inside. Our results are the first to demonstrate that plague bacteria are able to survive and replicate inside amoebae.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" srcset="https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=587&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=587&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=587&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=738&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=738&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/207700/original/file-20180223-108113-jcwgw8.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=738&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron microscope image of plague bacteria inside an amoeba. YP indicates <em>Yersinia pestis</em> (plague bacteria). The red lines indicate bacteria that appear to be replicating.</span>
<span class="attribution"><span class="source">David Markman</span></span>
</figcaption>
</figure>
<p>The next challenge is understanding how long plague bacteria can survive in amoebae. Part of an amoeba’s life cycle includes transforming into a cyst – a form in which it can <a href="http://dx.doi.org/10.1128/JCM.01903-08">lie dormant for up to 20 years</a> before it reanimates and resumes eating and multiplying. This enables it to survive during adverse environmental conditions, such as extreme temperatures or drought. If plague bacteria can survive inside dormant amoebae cysts for many years, this could explain how and where they persists between outbreaks.</p>
<h2>Amoebae as disease training grounds</h2>
<p>Amoebae are already recognized for their potential role in <a href="http://dx.doi.org/10.1128/CMR.17.2.413-433.2004">protecting</a>, <a href="http://dx.doi.org/10.1111/j.1469-0691.2009.03011.x">amplifying</a> or <a href="https://doi.org/10.1111/j.1574-6976.2009.00190.x">guiding</a> the evolution of over 225 other bacteria, viruses, and fungi. Famously, it is hypothesized that they played a role in the first known outbreak of <a href="https://doi.org/10.1016/j.clinmicnews.2010.11.001">Legionnaires’ disease</a> in 1976 by providing a protected space for <em>Legionella</em> bacteria to multiply. Amoebae can also act as transport vessels for pathogens, enabling the bacteria to enter and infect new hosts. </p>
<p>Some scientists hypothesize that amoebae can guide harmless bacteria to evolve into dangerous pathogens. The reasoning behind this is that amoebae are very similar to macrophages – the white blood cells in mammals that are responsible for finding and killing invading bacteria. If harmless soil bacteria evolve the ability to survive and multiply within amoebae, then they might also be able to do so in the white blood cells that comprise our immune system, thereby becoming new human pathogens.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" srcset="https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=402&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=402&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=402&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=505&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=505&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/207690/original/file-20180223-108146-nkc04l.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=505&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human plague cases and deaths in the United States, 2000-2016.</span>
<span class="attribution"><a class="source" href="https://www.cdc.gov/plague/maps/index.html">CDC</a></span>
</figcaption>
</figure>
<p>The idea of amoebae acting as “<a href="http://aem.asm.org/content/71/1/20">training grounds</a>” for the evolution of dangerous pathogens like plague conforms with what scientists already know about human plague infections. In human cases, plague is engulfed by white blood cells, but has <a href="http://dx.doi.org/10.3389/fcimb.2013.00106">evolved a way to avoid destruction</a> by escaping the portion of the cell responsible for digestion. Then it multiplies inside the white blood cell before exiting and disseminating throughout the human body. </p>
<p>This process is nearly identical to the process our research team observed in amoebae. Did this ability to avoid destruction and multiply within white blood cells – which is found in many human pathogens – arise from ancient soilborne bacteria learning to exploit amoebae? Perhaps practice really does make perfect.</p>
<p>Pathogen-harboring amoebae could be serious public health threats, since we currently have no way to efficiently monitor them in the environment or predict when they might release infectious agents. They may also pose a biosecurity threat that a hostile power could use to disperse existing pathogens or create new ones. We need more research on the complex interactions that allow pathogens to survive, disseminate and evolve so that we can learn to predict and prevent disease outbreaks and their consequences.</p><img src="https://counter.theconversation.com/content/90610/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Markman receives funding from the Department of Defense through the &quot;National Defense, Science, and Engineering Graduate Fellowship&quot; program.</span></em></p>Where do plague bacteria go between outbreaks? New research demonstrates that they can survive and replicate inside amoebae that are widely present in soil and water worldwide.David Markman, PhD Candidate, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/633632016-08-15T15:01:28Z2016-08-15T15:01:28ZWe're holding an amoeba Olympics to uncover the mechanisms behind human diseases<figure><img src="https://images.theconversation.com/files/133551/original/image-20160809-20932-1b39fuy.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Dictyostelium discoideum at work.</span> <span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/thumb/5/5a/Dictyostelium_discoideum_43.jpg/1280px-Dictyostelium_discoideum_43.jpg">Usman Bashir/Wikimedia</a></span></figcaption></figure><p>There are 10,000 competitors and a variety of events to test their abilities. You would be forgiven for thinking that I am about to talk about the Rio Olympics.</p>
<p>But approximately 5,600 miles away from the games, our lab in Cardiff will be training amoeba participants to take part in various tests – but rather than gold medals, the legacy of these competitions will be new understanding of human diseases, such as bacterial infections, cancer and psychiatric disorders. </p>
<p>Humans and amoeba are distant evolutionary cousins and rather fortuitously have comparable genetic makeups. In fact, the amoeba we are using, <em>Dictyostelium discoideum</em>, played an important role in finding the mechanism of the <a href="http://www.nature.com/nature/journal/v417/n6886/full/417292a.html">mood stabilising drug lithium</a>. Despite lithium having been used as a medicine to <a href="http://www.mind.org.uk/information-support/drugs-and-treatments/lithium-and-other-mood-stabilisers/about-lithium/#.V7GVHbgrLIU">treat psychiatric disorders</a> for more than a century, the way it worked was previously unknown. But now that the key pathway has been <a href="https://books.google.co.uk/books?id=BKwkonZwZD0C&amp;pg=PA264&amp;lpg=PA264&amp;dq=how+lithium+affects+amoeba&amp;source=bl&amp;ots=caKM53WxDW&amp;sig=bhXFsID7yhiCShQONfARXCukeGA&amp;hl=en&amp;sa=X&amp;ved=0ahUKEwjKl8evzrTOAhVDSBQKHWV4CvIQ6AEIMTAD#v=onepage&amp;q=how%20lithium%20affects%20amoeba&amp;f=false">found and characterised in amoeba</a>, and we know how these single-cell organisms are affected by it, researchers can move on to investigating how it works in human cells. </p>
<p><em>Dictyostelium discoideum</em> is a <a href="http://modelorganisms.nih.gov/d_discoideum/">soil-dwelling social amoeba</a>, more affectionately known as “Dicty”. Dicty was plucked from a forest in North Carolina in 1935 and now resides in hundreds of labs across the world. To date, it has helped us track the movement of neutrophils, one of the most abundant white blood cells in the human body; the mechanism behind the rare “smooth brain” disorder Lissencephaly; resistance to the cancer chemotherapy drug cisplatin; and infections of the harmful bacteria that cause Legionnaire’s disease and TB. </p>
<h2>Starting line</h2>
<p>Dicty won’t need to throw a javelin or run 100m to win an event: the winner will be the “athlete” who is able to multiply the fastest – although slow growth is just as interesting. Each one of the athletes has a unique feature to contend with; they are each missing a different gene, but otherwise they are all genetically identical. Without the gene, the cell will lose a specific function and so its performance will be affected. Thousands of amoeba with different function handicaps will be observed side-by-side. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/ShlCwqlCA4Y?wmode=transparent&amp;start=0" frameborder="0" allowfullscreen></iframe>
</figure>
<p>Our goal is to challenge the cells to grow in the presence of lithium and see which ones thrive and which struggle. By taking away a specific gene, we can see whether the amoeba performs better than its competitors who have other genes taken away.</p>
<p>We have spent the past two years bringing together and cultivating these miniature athletes for this project in a bid to create a powerful new resource for the scientific community. Shortly these tiny athletes will be put into stasis and shipped around the world to take part in competitions and help other researchers explore molecular mechanisms.</p>
<p>As the 2016 amoeba games open, the thousands of amoeba will be placed in about 3⅓ tablespoons of nutrient rich broth and compete simultaneously in the first lithium challenge. It is easy to imagine now that the whole human genome has been sequenced that we know the role of every A, T, C and G – but in truth our genome is vast and this is far from the case. We hope the winners (and the losers) will reveal further new components and pathways.</p>
<p>One key element that has made this possible today has been the affordability and capacity of next-generation sequencing technology. Less than £1,000 will buy us a mind-boggling 400m sequencing reads. Each amoeba has a unique athlete number and so can be detected by sequencing and counted. This would have been impossible 10 years ago, but it has now given us the ability to monitor thousands of individuals simultaneously and detect changes in abundance. Plus 400m sequencing reads is enough to run three heats so we will make sure the true winners reach the podium.</p>
<p>Each event will reveal how different genomes are affected in the presence of lithium and so help us study the processes of human health and disease. This simple yet powerful model organism will play an important role in discovering how our genomes function and allow us to develop better medications.</p><img src="https://counter.theconversation.com/content/63363/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Amy Baldwin is employed by a Wellcome Trust grant awarded to Cardiff University and The University of Manchester. </span></em></p>They may be single-celled organisms, but as our distant cousins amoeba can tell us a lot about ourselves.Amy Baldwin, Research associate, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/503872015-11-10T02:50:36Z2015-11-10T02:50:36ZExplainer: what are brain-eating amoebas and how can we reduce their harm?<figure><img src="https://images.theconversation.com/files/101357/original/image-20151110-29326-1x0ran6.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">The disease can only occur when contaminated water goes up into the nose.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-147704720/stock-photo-childes-hand-holding-hose-sprinklers-and-watering.html?src=-k25UL3V4qLzxb2YO0I49Q-1-1">Vladimir Gjorgiev/Shutterstock</a></span></figcaption></figure><p>Amoebas are ancient bugs that predate multicellular organisms and often hide in water and mud. Yesterday’s ABC <a href="http://www.abc.net.au/austory/">Australian Story</a> told the story of Jodi and Laine Keogh, whose one-year-old son Cash died from a rare, devastating disease caused by the amoeba <em>Naegleria fowleri</em>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=237&amp;fit=clip" srcset="https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=404&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=404&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=404&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=507&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=507&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/101287/original/image-20151109-29326-5deecf.jpeg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=507&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Amoebas are single-cell organisms that often live in water and mud.</span>
<span class="attribution"><a class="source" href="http://www.wikidoc.org/index.php/File:Amebiasis19.jpeg">Jesus Hernandez</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>This amoeba lives predominantly in warm freshwater and <a href="http://www.cdc.gov/parasites/naegleria/">occurs naturally</a> in northern Australia. </p>
<p>Infections were <a href="http://www.cdc.gov/parasites/naegleria/public-water-systems.html#r6">first detected</a> in the 1970s after exposure to solar-warmed water that was transported long distances through overland pipes. The heated water had low levels of disinfectant, which promoted the growth of <em>Naegleria fowleri</em>. Water distribution systems have since been regularly monitored for the amoeba. </p>
<p><em>Naegleria fowleri</em> has been <a href="http://gingin.wa.gov.au/images/assets/Uploads/Forms_Pamphlets/Amoeba%20fact%20sheet%20-%20Naegleria%20fowleri.pdf">labelled</a> the “brain-eating amoeba” because it can cause <a href="http://www.cdc.gov/parasites/naegleria/">primary amoebic meningoencephalitis</a> (PAM). This is an infection that leads to the destruction of brain tissue and is nearly always fatal. </p>
<p>This disease occurs <a href="http://www.ncbi.nlm.nih.gov/pubmed/19845995">mainly</a> in healthy active children and young adults exposed to warm fresh water. Most cases involve going to a swimming pool, freshwater lake or pond. Jodi and Laine Keogh’s son Cash likely contracted the bug via a garden hose. Boys and young men appear to be particularly susceptible to the infection. </p>
<p>Although antibiotics can kill off_ Naegleria fowleri_, successful treatment of human cases is rare due to <a href="http://www.ncbi.nlm.nih.gov/pubmed/8916161">the challenge of making</a> an early diagnosis. </p>
<p>There are some important points to know about <em>Naegleria fowleri</em>. First, you <a href="http://www.cdc.gov/parasites/naegleria/infection-sources.html">cannot get infected</a> from drinking water contaminated with <em>Naegleria fowleri</em>. The disease can only occur when contaminated water goes up into the nose. It certainly cannot be spread from one person to another. </p>
<p>Public water supplies in the <a href="http://health.nt.gov.au/library/scripts/objectifyMedia.aspx?file=pdf/45/25.pdf&amp;siteID=1&amp;str_title=Naegleria%20fowleri.pdf">Northern Territory</a> and <a href="http://conditions.health.qld.gov.au/HealthCondition/condition/14/165/101/Naegleria-fowleri-Qs-As">Queensland</a> are chlorinated to protect against <em>Naegleria fowleri</em>. However, rural and Indigenous communities <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/eh33.pdf">may not have ready access</a> to chlorinated water. Access to chlorinated water for drinking and washing in these regions then becomes a priority issue. </p>
<p>Other harm-reduction measures include boiling water for at least one minute, filtering water (using a filter with an absolute pore size of one micron or smaller), or drinking distilled water.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=237&amp;fit=clip" srcset="https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=400&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=400&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=400&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=503&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=503&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/101359/original/image-20151110-29321-1msmvyt.jpg?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=503&amp;fit=crop&amp;dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Boiling water for one minute can kill Naegleria fowleri.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-257821525/stock-photo-electric-glass-kettle-on-a-domestic-kitchen.html?src=K_lZx0AGN-DpY3gLB0MEpw-1-24">Lilyana Vynogradova/Shutterstock</a></span>
</figcaption>
</figure>
<p><a href="http://www.cdc.gov/parasites/naegleria/sinus-rinsing.html">Limiting the amount</a> of potentially contaminated water (from untreated water sources) going up the nose is also very important. </p>
<p>Infections from <em>Naegleria fowleri</em> are <a href="http://www.ncbi.nlm.nih.gov/pubmed/18820207">very rare</a>, with around 300 known deaths worldwide. Even though true death rates are likely to be higher because many infections are undiagnosed, it is considered a rare disease. </p>
<p>This contrasts with another amoebic organism, <em>Entamoeba histolytica</em>, which is <a href="https://www.mja.com.au/journal/2007/186/8/amoebiasis-current-status-australia">estimated to result</a> in 40,000 to 100,000 deaths a year worldwide. </p>
<p><em>Entamoeba histolytica</em> infects the large intestine and causes a type of gastroenteritis known as <a href="http://ideas.health.vic.gov.au/diseases/amoebiasis-facts.asp">amoebiasis</a>. This amoeba has a <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125031/">simple life cycle</a> and spreads when cysts in faeces contaminate food and water sources. </p>
<p>It <a href="http://iceh.uws.edu.au/fact_sheets/FS_amoebiasis.html">most commonly affects</a> young to middle-aged adults and is associated with poor sanitation. It is a frequent cause of diarrhoea among travellers to developing countries. </p>
<p>In most _Entamoeba histolytica _infections, symptoms are absent or very mild. These cases are <a href="http://www.ncbi.nlm.nih.gov/pubmed/12660071">known as</a> non-invasive disease. </p>
<p>In cases of invasive disease, symptoms include diarrhoea (which can contain blood), abdominal cramps and fever. Rarely, amoebiasis can cause a liver abscess. </p>
<p>Stool antigen testing is the <a href="http://cid.oxfordjournals.org/content/29/5/1117.long#ref-1">main method</a> used to diagnose intestinal infection. Prompt treatment with antibiotics can kill the bug. </p>
<p>Good personal hygiene is important for preventing amoebiasis. As with <em>Naegleria fowleri</em>, drinking water previously boiled for one minute or filtering water <a href="http://iceh.uws.edu.au/fact_sheets/FS_amoebiasis.html">greatly reduces</a> any contamination by <em>Entamoeba histolytica</em>.</p><img src="https://counter.theconversation.com/content/50387/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vincent Ho does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Amoebas are ancient bugs that predate multicellular organisms that often hide in water and mud.Vincent Ho, Lecturer and clinical academic gastroenterologist, Western Sydney UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/139792013-06-06T05:49:16Z2013-06-06T05:49:16ZWant a new epilepsy drug? Bring on the amoebas<figure><img src="https://images.theconversation.com/files/25114/original/qyms7695-1370456933.jpg?ixlib=rb-1.1.0&amp;rect=106%2C0%2C1066%2C654&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Feeling fruity: the amoeba Dictyostelium discoideum forms &#39;fruiting bodies&#39;</span> <span class="attribution"><span class="source">Robin Williams</span></span></figcaption></figure><p>Many therapeutic drugs and toxins affect us without us knowing exactly how. We know, for example, that Epilim, <a href="http://www.netdoctor.co.uk/brain-and-nervous-system/medicines/epilim.html">or sodium valproate</a>, one of the most highly prescribed medicines for epilepsy can prevent epileptic fits but little is known about how this works at a cellular level. </p>
<p>Knowing how drugs target and interact with our cells could have huge implications in medical research. It could help us to improve drug design and work out who will respond better to different treatments.</p>
<p>And the amoeba <em>Dictyostelium</em> <a href="http://www.ncbi.nlm.nih.gov/pubmed/16890490">in particular</a> can help. <em>Dictyostelium</em>, <a href="http://www.rhul.ac.uk/biologicalsciences/rdd/documents/pdf/posterpakes.pdf">known as a social amoeba</a> - previously referred to as slime mould - can be found growing in the soil, decaying leaves and wood in forests. Its life cycle takes it from a single cell organism that eats bacteria, to a “fruiting body” containing around 50,000 cells. Its simplicity makes it easy to study, and it can be grown in a lab and can be used to understand how medical drugs function on a molecular level.</p>
<p>In most kinds of studies that test toxicity, animals - and mammals especially - are used because their genetic composition and biochemistry is closely related to ours. But <em>Dictyostelium</em> can be a good substitute. It can be used to test chemicals and is both faster and cheaper than using animal cells.</p>
<h2>The drugs don’t work</h2>
<p>One interesting example of amoeba research is in the area of epilepsy treatment. Epilim is an anti-convulsant that prevents epileptic fits but is also used to treat a number of psychiatric conditions such as bipolar disorder (manic depression).</p>
<p>Around <a href="http://www.who.int/mediacentre/factsheets/fs999/en/index.html">50 million people</a> worldwide have epilepsy - <a href="http://www.epilepsy.org.uk/press/facts">600,000 in the UK</a> - but despite the development of better epilepsy treatments and the availability of a range of new treatments over the past 50 years, seizures still can’t be controlled in about a third of these. There’s a pressing need to develop and improve epilepsy treatments. </p>
<p>We used <em>Dictyostelium</em> to study how Epilim worked. By looking at how Epilim caused the chemical signals within each amoeba to change, we have shown that Epilim’s effect is related to the production or breakdown of a particular <a href="http://www.ncbi.nlm.nih.gov/pubmed/23177536">family of compounds containing a specific sugar called inositol</a>. Developing new drugs that are better at doing this may lead to improved treatments.</p>
<h2>New medicines could replace strict diet</h2>
<p>Children who have severe epilepsy that doesn’t respond to epilepsy drugs are often put on a MCT ketogenic diet. This means they have to eat foods that are high in specific fats and low in carbohydrates. The diet is thought to mimic some aspects of starvation by forcing the body to burn fats rather than carbohydrates - which is why the Atkins diet became popular with people wanting to lose weight. But the diet is a gruelling one and can have nasty side-effects including constipation and reduced growth. </p>
<p>Our work with amoeba has helped us identify a fatty acid which plays a key role in how the MCT ketogenic diet prevents seizures. Research has shown an increase in the amount of this fatty acid <a href="http://www.ncbi.nlm.nih.gov/pubmed/23177536">in children’s blood</a> when on the diet. This fatty acid is more potent at controlling seizures (in animal models of seizures and epilepsy) than Epilim. Making this link between the diet, the fatty acid, and seizure control could provide the first steps in developing a new drug that replaces the diet.</p>
<p>Also promising is the discovery of new compounds identified using amoeba that could prove even better than Epilim in preventing seizures. These compounds are much more potent than Epilim and can block seizures, but do not have the side effects associated with Epilim, making them both more potent and safer.</p>
<p>There’s some way to go but amoebas are helping us to discover new things. <em>Dictyostelium</em> can also help us discover more about the role that chemical compounds play in treating Alzheimer’s disease <a href="http://www.ncbi.nlm.nih.gov/pubmed/15950352">and Bipolar Disorder</a>.</p><img src="https://counter.theconversation.com/content/13979/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robin Williams has received funding from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3R), Dr Hadwen Trust for Humane Research. He has a submitted a patent for a new treatment for epilepsy</span></em></p>Many therapeutic drugs and toxins affect us without us knowing exactly how. We know, for example, that Epilim, or sodium valproate, one of the most highly prescribed medicines for epilepsy can prevent…Robin Williams, Professor of Molecular Cell Biology, Royal HollowayLicensed as Creative Commons – attribution, no derivatives.